Immunology has made a remarkable progress in recent years and has added a great contribution to the field of medicine.
Studies of immunology have revealed that cytokines produced by macrophages, lymphocytes, etc. play the central role in promoting or suppressing every immunological reaction, such as infection immunity, tumor immunity, allergies, or anaphylaxis.
Mosmann and Coffman, et al. classified CD4.sup.+ T-cell clones which are established from mouse spleen cells and can be cultured for a long period of time into two different types of subsets according to the difference between cytokines produced by the clones (Mosmann, T. R., et al., J. Immunol., 136, 2348 (1986)).
Specifically, they classified CD4.sup.+ T-cell clones into the "T-helper 2 (Th2) subset" and the "T-helper 1 (Th1) subset": the former principally produces IL(interleukin)-4, IL-5, IL-6, IL-10 and IL-13; and the latter principally produces IL-2, IFN (interferon)-.gamma., and TNF (tumor necrosis factor)-.beta..
Although the existence of such subsets of helper T cells in humans was initially deemed dubious, it is now well accepted (Romagnani, S., Immunology Today 12, 256 (1991), etc.).
Nowadays, the nature and functions of the helper T-cell subsets Th2 and Th1 in mice or humans are becoming much more evident. In terms of biological significance, they have become of great interest as dominant cells which control different immunological reactions.
In many infectious diseases or immunological diseases, polarization is observed in the distribution of the Th1/Th2 subsets of lymphocytes of patients; i.e., an extreme bias arises in the distribution toward either one of the subset Th1 or Th2. Therefore, it is suggested that the nature of this polarization phenomenon may reflect the condition and type of the disease.
For example, the following are currently becoming distinct:
(1) In the case of Mycobacterium diseases, if immunological reactions with respect to Mycobacterium are mainly delayed-type hypersensitivity (DTH) reactions, the Th1 subset is dominant, whereas if the immunological reactions are chronic and progressive, the Th2 subset is dominant. (2) In the case of HIV diseases, the production of Th1-type cytokines is observed among many long-term nonprogressive HIV-infected patients. If polarization arises toward the Th2 subset, the symptoms of the diseases become progressive or fulminated. (3) With regard to patients having atopic diseases, if there arises polarization toward the Th2 subset, the diseases become aggravated.
In view of the foregoing, the problems to be solved by the present invention is to provide means for specifying the condition and type of immune-related diseases on the basis of the knowledge about the polarization of the distribution of Th1/Th2 subsets (hereinafter referred to as Th1/Th2 imbalance).